A critical need exists for the non-invasive and early identification of diseases. Optical biopsy using spectroscopic instruments offers a means to determine tissue pathology immediately and without the need for surgical biopsy. We propose to develop two spectroscopic systems for noninvasive detection and margin demarcation: 1) a depth sensitive fiber probe (Aim 1) a hyper spectral spectroscopic system (Aim 2). We will develop a depth-sensitive optical fiber probe to measure depth-dependent optical signatures. We will develop a spectroscopic system to translate probe based optical biopsy to a spectral format. These instrument systems can be used in concert to survey wide areas of tissue with the hyper-spectral spectroscopic device and then provide a detailed depth-sensitive analysis with the probe. We will use skin cancer as a model system to test the new spectroscopic instrument. For example, early identification of cancer increases patient survival while non-invasive and rapid identification of cancer will decrease morbidity. Of particular importance is the depth of a malignancy which is often used to stage disease (e.g. carcinoma in situ vs. invasive carcinoma). We will determine the sensitivity and specificity of each device compared to standard histopathology in a clinical pilot study (Aim 3). PUBLIC HEALTH RELEVANCE: There is a critical need for the development of less invasive portable technologies. Over the past decade, optical spectroscopy has been developed to assess tissue pathology and has been shown to provide detailed morphological and biochemical information without tissue removal. This quantitative information can be used to make a final diagnosis (a so called spectral diagnosis) similar to a pathologist using histology. A spectral diagnosis (SD) is non- invasive, does not require biopsy, fixation, processing or microscopic examination of tissue. The proposed project represents an interdisciplinary effort to develop technologies for the non- invasive detection of skin cancers. Such technologies offer the possibility to reduce morbidity and mortality associated with skin malignancy.